Metal scavenger

A method of treating and/or alleviating and/or preventing diseases and/or conditions chosen from the group consisting of autoimmune diseases, neurological diseases, fibromyalgia, chronic fatigue syndrome, chronic obstructive pulmonary disease (COPD), chronic bronchitis, pulmonary hypertension, hypertrophic cardiomyopathia, depression, anxiety disorders, general anxiety disorder, panic disorder, amyotrophic lateral sclerosis (ALS), Parkinson's disease, multiple sclerosis (MS), dementia, and heavy metal poisoning in a subject, the method comprising administering a scavenger to the subject, wherein the scavenger comprises a compound according to Formula I coupled to a carrier resin,

• wherein
• m, n, o and p independently from each other are 2 or 3;
• q is 1 or 2;
• X is —S— or >N(˜);
• and
• A is >CH(CH2O—) when X is —S—, and A is —CH2— when X is >N(˜);
• wherein ˜ represents a bond, optionally via a linker, to the carrier resin;
• and
• > denotes bonds within Formula I;
• and
• wherein the carrier resin is chosen from the group consisting of polystyrene, alkylidene-polystyrene, polystyrene comprising polyethylene glycol moieties, alkylidene-polystyrene comprising polyethylene glycol moieties, crosslinked polyvinyl alcohol, and polyacrylates.

A composition comprising a first and a second scavenger, wherein each scavenger comprises a compound according to Formula I coupled to a carrier resin,

• wherein
• m, n, o and p independently from each other are 2 or e
• q is 1 or 2;
• X is —S— or >N(˜);
• and
• A is >CH(CH2O—) when X is —S— and A ix —CH2— when X is >N(˜);
• wherein ˜ represents a bond, optionally via a linker, to the carrier resin;
• and
• > denotes bonds within Formula I;
• and
• wherein the carrier resin is chosen from the group consisting of polystyrene, alkylidene-polystyrene, polystyrene comprising polyethylene glycol moieties, alkylidene-polystyrene comprising polyethylene glycol moieties, crosslinked polyvinyl alcohol, and polyacrylates.

A kit comprising a first scavenger and a second scavenger, wherein each scavenger comprises a compound according to Formula I coupled to a carrier resin,

• wherein
• m, n, o and p independently from each other are 2 or 3;
• q is 1 or 2
• X is —S— or >N(˜);
• and
• A is >CH(CH2O—) when X is —S—, and A is —CH2— when X is >N(˜);
• wherein ˜ represents a bond, optionally via a linker, to the carrier resin;
• and
• > denotes bonds within Formula I;
• and
• wherein the carrier resin is chosen from the group consisting of polystyrene, alkylidene-polystyrene, polystyrene comprising polyethylene glycol moieties, alkylidene-polystyrene comprising polyethylene glycol moieties, crosslinked polyvinyl alcohol, and polyacrylates;
• wherein
• in the first scavenger, the carrier resin is polystyrene comprising polyethylene glycol moieties (PEG-polystyrene);
• and
• in the second scavenger, the carrier resin is alkylidene-polystyrene, the alkylidene-polystyrene being methylene-polystyrene.

A method for removing one or more heavy metal compounds from a body fluid, wherein the method comprises the steps of:

• (a) bringing the body fluid into contact with a first scavenger;
• (b) allowing the heavy metal compounds to bind to the first scavenger;
• and
• (c) removing the first scavenger from the body fluid;
• wherein the first scavenger comprises a compound according to Formula I coupled to a carrier resin,
• wherein
• m, n, o and p independently from each other are 2 or 3;
• q is 1 or 2;
• X is —S— or >N(˜);
• and
• A is >CH(CH2O—) when X is —S—, and A is —CH2— when X is >N(˜);
• wherein ˜ represents a bond, optionally via a linker, to the carrier resin;
• and
• > denotes bonds within Formula I;
• and
• wherein the carrier resin is chosen from the group consisting of polystyrene, alkylidene-polystyrene, polystyrene comprising polyethylene glycol moieties, alkylidene-polystyrene comprising polyethylene glycol moieties, crosslinked polyvinyl alcohol, and polyacrylates.

A device for removing a heavy metal from the blood of a subject, wherein the device comprises a first container having an inlet and an outlet;

• and wherein the first container encompasses a first scavenger, wherein the first scavenger comprises a compound according to Formula I coupled to a carrier resin,
• wherein
• m, n, o and p independently from each other are 2 or 3;
• q is 1 or 2;
• X is —S— or >N(˜);
• and
• A is >CH(CH2O—) when X is —S—, and A is —CH2— when X is >N(˜);
• wherein ˜ represents a bond, optionally via a linker, to the carrier resin;
• and
• > denotes bonds within Formula I;
• and
• wherein the carrier resin is chosen from the group consisting of polystyrene, alkylidene-polystyrene, polystyrene comprising polyethylene glycol moieties, alkylidene-polystyrene comprising polyethylene glycol moieties, crosslinked polyvinyl alcohol, and polyacrylates.

A method of preparation of a scavenger comprising a compound according to Formula I coupled to a carrier resin,

• wherein
• m, n, o and p independently from each other are 2 or 3;
• q is 1 or 2;
• X is —S—;
• and
• A is >CH(CH2O—);
• wherein ˜ represents a bond, optionally via a linker, to the carrier resin;
• and
• > denotes bonds within Formula I;
• wherein the carrier resin is chosen from the group consisting of polystyrene comprising polyethylene glycol moieties, alkylidene-polystyrene comprising polyethylene glycol moieties, crosslinked polyvinyl alcohol, and polyacrylates wherein the method comprises the steps of:
• (a) providing a solution of 1,2-dimercaptopropan-3-ol and a compound according to Formula II,
• MsO—(CH2)r—S—(CH2)s—S—(CH2)t—S—(CH2)u—OMs Formula II
• wherein r, s, t, and u independently of each other are 2 or 3,
• in a polar aprotic solvent;
• (b) providing a solution of a non-nucleophilic base in a polar aprotic solvent;
• (c) adding the solution of step (a) to the solution of step (b) over a time period of 24 h or longer, while heating the mixture to a temperature of 50-150° C.;
• (d) removing the solvents;
• (e) purifying the compound according to Formula I;
• and
• (f) coupling the compound according to Formula I to the resin.